PD-L1 expression in GI cancer and Immune checkpoint inhibitor

• Project/Area Number: 16K10511
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Fukushima Medical University
• Principal Investigator: Kono Koji 福島県立医科大学, 医学部, 教授 (40283204)
• Co-Investigator(Kenkyū-buntansha): 中島 隆宏 福島県立医科大学, 医学部, 博士研究員 (90567447)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
• Keywords: 免疫チェックポイント阻害 / 消化器癌 / Nivolmab / PD-L1 / 免疫チェックポイント阻害剤 / 消化器がん / 免疫チェックポイント / 免疫チョックポイント阻害剤 / IFN-gamma / 癌免疫療法 / PDL1 / PD1

Outline of Final Research Achievements

(I)PD-L1 is upregulated by IFN-g through JAK-STAT pathway in GI-tract cancer.(II)There is a positive correlation between EMT status and PD-L1 expression in GI tract cancer.(III)microRNA from tumor microenvironment can down-regulate PD-L1 expression in colon cancer

Academic Significance and Societal Importance of the Research Achievements

消化器癌におけるPD-L1の発現調節機構を解明することで、免疫チェックポイント阻害剤の効果増強、ResponderのPrediction、Non-responderの機序解明に寄与できる。

Research Products

• [Journal Article] microRNA-148a-3p regulates immunosuppression in DNA mismatch repair-deficient colorectal cancer by targeting PD-L1 (2019)
  • Author(s): Ashizawa Mai、Okayama Hirokazu、Ishigame Teruhide、Thar Min Aung Kyi、Saito Katsuharu、Ujiie Daisuke、Murakami Yuko、Kikuchi Tomohiro、Nakayama Yuko、Noda Masaru、Tada Takeshi、Endo Hisahito、Fujita Shotaro、Sakamoto Wataru、Saito Motonobu、Saze Zenichiro、Momma Tomoyuki、Ohki Shinji、Mimura Kosaku、Kono Koji
  • Journal Title: Molecular Cancer Research Volume: Epub ahead of print Issue: 6 Pages: 1403-1413
  • DOI: 10.1158/1541-7786.mcr-18-0831
  • Peer Reviewed / Open Access
• [Journal Article] Phospho-STAT1 expression as a potential biomarker for ant-PD-1/anti-PD-L1 immunotherapy for breast cancer. (2019)
  • Author(s): Nakayama Y, Mimura K, Tamaki T, Shiraishi K, Kua LF, Koh V, Ohmori M, Kimura A, Inoue S, Okayama H, Suzuki Y, Nakazawa T, Ichikawa D, Kono K.
  • Journal Title: Int J Oncol. Volume: 54 Pages: 2030-2038
  • DOI: 10.3892/ijo.2019.4779
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] PD-L1 expression is mainly regulated by IFN-γ associated with JAK-STAT pathway in gastric cancer (2018)
  • Author(s): Mimura Kousaku, TEH Jun, Okayama Hirokazu, Shiraishi Kensuke, Kua Ley-Fang, Koh Vivien, Smoot Duane T, Ashktorab Hassan, Oike Takahiro, Suzuki Yoshiyuki, Fazreen Zul, Asuncion Bernadette, Shabbir Asim, Yong Wei Peng, So Jimmy, Soong Richie and Kono, Koji.
  • Journal Title: Cancer Science Volume: 109 Pages: 43-53
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Epithelial-mesenchymal transition-converted tumor cells can induce T-cell apoptosis through upregulation of programmed death ligand 1 expression in esophageal squamous cell carcinoma (2018)
  • Author(s): 15.Thar Min AK, Okayama H, Saito M, Ashizawa M, Aoto K, Nakajima T, Saito K, Hayase S, Sakamoto W, Tada T, Hanayama H, Saze Z, Momma T, Ohki S, Sato Y, Motoyama S, Mimura K, Kono K.
  • Journal Title: Cancer Medicine Volume: 7 Pages: 3321-3330
  • NAID: 120007126995
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 消化器癌におけるPD-L1発現調節機構の解明 (2017)
  • Author(s): 三村耕作、河野浩二
  • Organizer: 日本外科学会
  • Place of Presentation: 横浜
  • Year and Date: 2017-04-26
• [Presentation] Regulatry mechanisms of PD-L1 on GI cancer (2016)
  • Author(s): Koji KONO
  • Organizer: 2017 annual meeting of Singapore Gastric Cancer Consocium
  • Place of Presentation: Singapore
  • Year and Date: 2016-07-20
  • Int'l Joint Research / Invited